title: Polymorphisms of MRP2 (ABCC2) are associated with susceptibility to nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  We hypothesized that ABCC2 gene variants may contribute to susceptibility to nonalcoholic fatty liver disease (NAFLD). Additionally, we tested the hypothesis of a relation between gene variants and disease severity.
  
  
  METHODS
  The study involved 167 individuals: 109 consecutively presenting unrelated patients with features of NAFLD and different stages of disease severity, and a group of 58 healthy individuals. Four tag single-nucleotide polymorphisms (SNPs; rs717620 A/G, rs2756105 C/T, rs2002042 C/T and rs3740066 A/G) representing 46 polymorphic sites (r(2)>.8) were genotyped. Furthermore, two additional SNPs (rs17222723 A/T and rs8187710 G/A) were included.
  
  
  RESULTS
  On univariate analysis, after multiple comparison correction by permutation tests, there were significant differences observed in the allele frequencies of rs17222723 and rs8187710 between healthy individuals and NAFLD patients (empirical P=.037 and .035, respectively). Allelic odds ratios [95% confidence interval] for rs17222723 and rs8187710 were 2.80 [1.11-7.04] and 2.80 [1.11-7.04], respectively. When we tested the hypothesis of a relation between gene variants and the clinical and histological spectra of NAFLD by multinomial regression analysis, a significant association was observed with the same markers: rs17222723 (P=.0029) and rs8187710 (P=.015).
  
  
  CONCLUSIONS
  Our study suggests a potential role of ABCC2 in susceptibility to NAFLD and disease severity.
authors.affiliation: Molecular Genetics and Biology of Complex Diseases Department, Institute of Medical Research A. Lanari, University of Buenos Aires-CONICET, 1427-Ciudad Autónoma de Buenos Aires, Argentina. ssookoian@lanari.fmed.uba.ar
authors.forename: Silvia
authors.initials: S
authors.lastname: Sookoian
authors.forename: Gustavo
authors.initials: G
authors.lastname: Castaño
authors.forename: Tomas Fernández
authors.initials: TF
authors.lastname: Gianotti
authors.forename: Carolina
authors.initials: C
authors.lastname: Gemma
authors.forename: Carlos Jose
authors.initials: CJ
authors.lastname: Pirola
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human